Randomized phase II study of clofarabine-based consolidation for younger adults with acute myeloid leukemia in first remission

Xavier Thomas, Stéphane De Botton, Sylvie Chevret, Denis Caillot, Emmanuel Raffoux, Emilie Lemasle, Jean Pierre Marolleau, Céline Berthon, Arnaud Pigneux, Norbert Vey, Oumedaly Reman, Marc Simon, Christian Recher, Jean Yves Cahn, Olivier Hermine, Sylvie Castaigne, Karine Celli-Lebras, Norbert Ifrah, Claude Preudhomme, Christine TerréHervé Dombret

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    Résumé

    Purpose To evaluate the efficacy and safety of a clofarabine-based combination (CLARA) versus conventional high-dose cytarabine (HDAC) as postremission chemotherapy in younger patients with acute myeloid leukemia (AML). Patients and Methods Patients age 18 to 59 years old with intermediate- or unfavorable-risk AML in first remission and no identified donor for allogeneic stem-cell transplantation (SCT) were eligible. Two hundred twentyone patients were randomly assigned to receive three CLARA or three HDAC consolidation cycles. The primary end point was relapse-free survival (RFS). To handle the confounding effect of SCT that could occur in patients with late donor identification, hazard ratios (HRs) of events were adjusted on the time-dependent treatment X SCT interaction term. Results At 2 years, RFS was 58.5% (95% CI, 49% to 67%) in the CLARA arm and 46.5% (95% CI, 37% to 55%) in the HDAC arm. Overall, 110 patients (55 in each arm) received SCT in first remission. On the basis of a multivariable Cox-adjusted treatment X SCT interaction, the HR of CLARA over HDAC before or in absence of SCT was 0.65 (95% CI, 0.43 to 0.98; P = .041). In a sensitivity analysis, when patients who received SCT in first remission were censored at SCT time, 2-year RFS was 53.3% (95% CI, 39% to 66%) in the CLARA arm and 31.0% (95% CI, 19% to 43%) in the HDAC arm (HR, 0.63; 95% CI, 0.41 to 0.98; P = .043). Gain in RFS could be related to the lower cumulative incidence of relapse observed in the CLARA arm versus the HDAC arm (33.9% v 46.4% at 2 years, respectively; cause-specific HR, 0.61; 95% CI, 0.40 to 0.94; P = .025). CLARA cycles were associated with higher hematologic and nonhematologic toxicity than HDAC cycles. Conclusion These results suggest that CLARA might be considered as a new chemotherapy option in younger patients with AML in first remission.

    langue originaleAnglais
    Pages (de - à)1223-1230
    Nombre de pages8
    journalJournal of Clinical Oncology
    Volume35
    Numéro de publication11
    Les DOIs
    étatPublié - 10 avr. 2017

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